title: The impact of manufacturing variables on in vitro release of clobetasol 17-propionate from pilot scale cream formulations.
abstract: OBJECTIVE
  The purpose of the study was to evaluate the effect of different homogenization speeds and times, anchor speeds and cooling times on the viscosity and cumulative % clobetasol 17-propionate released per unit area at 72 h from pilot scale cream formulations. A 2(4) full factorial central composite design for four independent variables were investigated.
  
  
  METHODS
  Thirty pilot scale batches of cream formulations were manufactured using a Wintech® cream/ointment plant. The viscosity and in vitro release of CP were monitored and compared to an innovator product that is commercially available on the South African market, namely, Dermovate® cream.
  
  
  CONCLUSIONS
  Contour and three-dimensional response surface plots were produced and the viscosity and cumulative % CP released per unit area at 72 h were found to be primarily dependent on the homogenization and anchor speeds. An increase in the homogenization and anchor speeds appeared to exhibit a synergistic effect on the resultant viscosity of the cream whereas an antagonistic effect was observed for the in vitro release of CP from the experimental cream formulations. The in vitro release profiles were best fitted to a Higuchi model and diffusion proved to be the dominant mechanism of drug release that was confirmed by use of the Korsmeyer-Peppas model.
  
  
  CONCLUSIONS
  The research was further validated and confirmed by the high prognostic ability of response surface methodology (RSM) with a resultant mean percentage error of (±SD) 0.17 ± 0.093 suggesting that RSM may be an efficient tool for the development and optimization of topical formulations.
authors.affiliation: Faculty of Pharmacy, Rhodes University , Grahamstown , South Africa.
authors.forename: Ayeshah Fateemah Beebee
authors.initials: AF
authors.lastname: Fauzee
authors.forename: Sandile Maswazi
authors.initials: SM
authors.lastname: Khamanga
authors.forename: Roderick Bryan
authors.initials: RB
authors.lastname: Walker
mesh_terms: D000287:Administration, Topical; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002990:Clobetasol / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D010865:Pilot Projects; D063465:Skin Cream / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
chemical_list: D002990:Clobetasol
keywords: Anchor speed; corticosteroids; homogenization speed; release kinetics; response surface methodology; topical formulations; viscosity